Lamotrigine for Bipolar Disorder

[0:07]But again, then, how slow is lamotrigine? Like you see that patient who's got a severe depression and you want this to work fast. How slow is lamotrigine? It has the reputation for being because of its long titrations, 6-8 weeks depending on how you do it. So it has a reputation for being slow. I've heard people say, well, we don't use lamotrigine on our inpatient psychiatric unit because it's too slow, which strikes me as rather ironic because, wait a minute. Don't you start anti-depressants on your inpatient psychiatric unit? Well, we all expect that a full trial of an antidepressant to rule whether it's effective or not, can take six, or some people would even say eight weeks. So if it makes sense to start an antidepressant on an inpatient unit, it certainly makes sense to start lamotrigine on an inpatient unit. Nevertheless, it does have this reputation for being slow. In fact, so people go on and use something that they think is faster, like quetiapine, say, or even lithium. Well, so, the irony is that lamotrigine is not so slow to produce a benefit. So, there was a randomized trial in which it went head-to-head with olanzapine fluoxetine combination. The study was sponsored by Eli Lilly, who make olanzapine fluoxetine combination. So you would expect that maybe they would kind of stack the deck against lamotrigine, and they did, in a number of interesting ways. Olanzapine fluoxetine got to start faster, lamotrigine had to do its usual titration, but interestingly, even though lamotrigine was always less effective than the olanzapine fluoxetine combination, it was never as good. But it was just as fast as the combination. In other words, the curve of improvement is not quite superimposed on that of a lanxapine fluoxetine combination. It's parallel to it from the very beginning. So instead of waiting and waiting and waiting and then finally it kicks in. No, the benefits were paralleling the improvement on a lanzapine fluoxetine combination, just not quite as good. So, it's not that slow, at least based on that study. So I think it makes sense to start lamotrigine where you would think of starting an antidepressant. It's not that slow. Now, in severe bipolar depression, if the patient's life is at stake, and using a treatment with robust evidence for efficacy instead of lamotrigine would make sense. Like electroconvulsive therapy, ECT for example, or maybe quetiapine, which can be quite fast, or maybe even olanzapine fluoxetine combination, because the evidence for efficacy for those agents is better. And patients in the middle of the mood spectrum can have depressions that are this severe. But patients in that middle of the spectrum, they will likely have had these depressions many times before, and they face the prospect of having them again unless a treatment is found that will prevent recurrences, in other words, a maintenance agent. So, unless the depression is immediately dangerous, to me, it does not make sense to hurry toward a treatment with significant side effects like memory impairment with ECT, or metabolic risks with quetiapine or olanzapine. And skip over in the process a treatment with few side effects and no established long-term risks. Most patients in my practice prefer to work their way through options starting with those, that if they work, will be the most tolerable in the long run, even if the likelihood of response is lower. If lamotrigine doesn't work in six weeks when you've reached at least 100 milligrams, okay, then, move on. To summarize, key points here, lamotrigine is not much slower than antidepressants to produce benefits. But if the patient has dangerous severe symptoms, use something that's likely to be faster, like ECT or olanzapine fluoxetine combination, even though I think lamotrigine's not far behind on that one. And otherwise, patients, again, they tend to choose based on tolerability, not speed.